Consumption of psychoactive substances has been important in the lives of indigenous American people for several millennia. While numerous studies have reported the occurrence of smoking pipes at archaeological sites, only a few have addressed the question of the substances being smoked. The study of smoking pipes is of particular interest at the Early Ceramic period archaeological site La Granja in central Chile (500e1000 A.D.) given its ritual connotation. Analysis by gas chromatography coupled to mass spectrometry showed the presence of nicotine in a large proportion of the residues extracted from a wide variety of grinding and smoking artifacts from La Granja (total N ¼ 116). Additionally, the likelihood of finding residual nicotine varied along pipe segments, decreasing from the bowl to the mouthpieces. This research has studied the cultural operative chain of the smoking complex of the Early Ceramic period of central Chile and described Nicotiana sp. as a plausible plant source with nicotine as the compound involved in the physiological effect, micromortars and pestles as the artifacts used in the preparation of plants for smoking and finally, the smoking pipe through which the plant compounds were incorporated into the smoker’s organism.